P638: THE RISK OF SECOND PRIMARY MALIGNANCIES AND CAUSE-SPECIFIC MORTALITY AMONG PATIENTS WITH T-CELL PROLYMPHOCYTIC LEUKEMIA IN THE UNITED STATES: A POPULATION-BASED STUDY.
Authors: K. Chamarti, M. Mannem, B. Bakhati
Journal: HemaSphere (2022)

Background: T cell prolymphocytic leukemia (T-PLL) is a rare lymphoid malignancy, compromising 2% of mature lymphocytic leukemias. The T-PLL follows an aggressive clinical course with median survival of 7.5 months with conventional chemotherpay. In the era of targeted therapy with anti-CD52 antibody for patients with T-PLL, there is data lacking on the spectrum of second primary malignancies (SPMs) and cause-specific mortality. Aims: In this current study we aim to identify the risk of SPM and cause specific mortality in patients with T-PLL in the era of targeted therapies with anti-CD52 antibodies using a national registry from the United States. Methods: The incidence of SPMs and cause-specific mortality among two-month survivors of T-PLL, was estimated using the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER)-13 registries. We included patients from 1992-2018 with ICD-O-3 code 9834/3 from the registry. We estimated the risk of SPMs using standardized incidence ratios (SIRs) and cause-specific mortality by standardized mortality ratios (SMRs) and absolute excess risk (AER)/10,000 population. Results: We included a total of 314 patients with T-PLL in this study. The median age at diagnosis was 68.5 years (range 1-85 years). The median follow-up duration was 12 months (range 0-196 months). A total of 13 (4%) patients developed 14 SPMs at the last follow-up. The SPM risk for the cohort was significantly elevated (SIR 2.54, 95% confidence interval [CI] 1.39-4.27) compared with general population. The median latency period for SPM development was 28 months (range 8-108 months). The SIR was significant among males (SIR 2.96, 95% CI 1.42-5.44), but not in females (SIR 1.88, 95% CI 0.51-4.82). The SIR according to age groups was significant in patients with age < 60 years (SIR 3.84, 95% CI 1.25-8.97), but not in age > 60 years (SIR 2.14, 95% CI 0.98-4.06). Specific SPMs with the highest risk included nasopharyngeal cancers (SIR 200.87, 95% CI 5.09-1,119.20) and multiple myeloma (SIR 33.39, 95% CI 6.89-97.58). At last follow-up, 155 (49%) patients had died, of which 89% were due to malignant neoplasms. There was statistically significant risk of mortality due to all malignant cancers combined (SMR 58.35, 95% CI 49.03-68.94), largely due to mortality from lymphocytic leukemia (SMR 2587, 95% CI 2021-3264, AER 1757), non-Hodgkin lymphoma (SMR 100, 95% CI 45.88-190.45, AER 220), stomach and duodenal ulcers (SMR 73.74, 95% CI 1.87-410.84, AER 24.43), uterine cancer (SMR 66.55, 95% CI 1.68-370.78, AER 24.39), and pneumonia and influenza (SMR 11.88, 95% CI 2.45-34.71, AER 68.04). The risk of death from lymphocytic leukemia was highest within the first year of diagnosis of T-PLL and continued to decline slowly thereafter, although it remained statistically significantly elevated more than other causes of death (SMR 1yr=3405, AER 2666; SMR 1-5 yrs=2623, AER 1715; SMR 5-10 yrs=1015, AER 516). Summary/Conclusion: Our study reveals that the risk of developing SPMs remains elevated in patients with T-PLL compared to the general population. Additionally, men are at an increased risk for SPMs compared to women. Despite therapeutic advances in T-PLL, hematologic neoplasms (including lymphocytic leukemia) have remained the leading cause of death in the last three decades. Further studies are needed to better define the healthcare needs of T-PLL patients beyond initial treatment to reduce the burden of mortality from T-PLL and other SPMs.